By the staff of ASCO Post
Posted: 2022-10-18 14:30:00
Researchers have found that the organization of different types of immune cells in pancreatic tumors may be related to how well pancreatic cancer patients respond to treatment and how long they survive. According to the data provided by Mi et al cancer research.
“Mapping the location of certain immune cells associated with a tumor could be a new biomarker to predict a patient’s survival,” he said Aleksander S Popel, PhD, Professor of Biomedical Engineering and Director of the Systems Biology Laboratory at Johns Hopkins University School of Medicine and a member of the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center. “We hope that our results will not only lead to a better fundamental understanding of cancer, but also [to] the potential to provide prognostic guidance to clinicians treating pancreatic cancer.”
The National Cancer Institute (NKI) It is estimated that by the end of 2022, more than 62,000 Americans will be diagnosed with pancreatic cancer and nearly 50,000 will die from the disease. On average, only about 10% of people with pancreatic cancer survive 5 years. It is difficult to predict which patients are most likely to respond to the few existing treatments; Researchers have long searched for additional cells, molecules, or genes that might help stratify pancreatic cancer patients by survival.
In recent years, scientists who have studied many types of cancer have discovered the importance of the non-cancerous cells, molecules, and blood vessels that surround tumors, collectively referred to as the tumor microenvironment. Part of this tumor microenvironment consists of immune cells; Some have the ability to attack a tumor for destruction, while others help the tumor evade the immune system.
In previous studies of pancreatic cancer, researchers counted how many immune cells were present in the tumor microenvironment and found no correlation with patient outcomes, but Dr. Popel and colleagues hypothesized that the physical arrangement of the immune cells might be more important than the total number.
In the new study, researchers used a method called multiplex immunohistochemistry to determine the locations of 27 different immune molecules in surgically resected tumors from 45 people with pancreatic ductal adenocarcinoma. The patients – 52% of whom were women, with an average age of 63.5 years – had all stages of cancer, with 41% of the participants having spread to at least four lymph nodes.
The molecules found in different combinations on the surfaces of different immune cell types corresponded to the relative positions of the immune cell subtypes.
The researchers then developed new computational algorithms to analyze how these cells differed in number, location and shape between patients who survived longer or shorter than the median survival time of 619 days.
“With the computational approaches we developed, we not only analyzed the density of each cell type, but also how they interact with each other in the spatial architecture of the tumors,” said the first author of the study Haoyang Mi, MDa graduate student in the Department of Biomedical Engineering at Johns Hopkins University School of Medicine.
The researchers discovered that among the 22 patients who survived shorter than the average time (a median survival time of 313 days), immune cells called IL-10-positive myelomonocytes tended to be located near a cluster of granzyme B-positive CD8 positive T cells (or cytotoxic T lymphocytes). Among the 23 patients who survived longer than average (a median survival time of 832 days), the same myelomonocytes were clustered more closely near a different type of T cell, identified as PD-1+ CD4+ T cells ( or activated helper T cells) are known ).
Given what is known about the function of each of these immune cells, the results make sense, said Dr. Wed. Each cell type acted like a brake on another. Cytotoxic T lymphocytes produced a toxin that can kill cancer cells, but the researchers hypothesized that nearby myelomonocytes blocked this ability in patients who survived shorter than average. However, in patients who survived longer than average, the researchers suggested that the activated helper T cells knocked out the myelomonocytes, which in turn allowed the cytotoxic T lymphocytes to fight the cancer more effectively.
More studies are needed to test hypotheses about how the cells in the pancreatic tumor microenvironment interact, the researchers said, and to determine whether targeting one of the cell types could lead to new immunotherapies for pancreatic cancer. However, the researchers expressed hope that additional studies will confirm that the link between the tumor microenvironment and survival can provide clinicians with prognostic information and potentially guide patients to specific treatments or clinical trials.
Disclosure: This study was supported by the National Institutes of Health (NIH), the Knight Cancer Institute and the Brenden-Colson Center for Pancreatic Care at Oregon Health & Sciences University. For full disclosures by study authors, visit aacrjournals.com.
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